Mitochondrial dna copy number and exposure to polycyclic aromatic hydrocarbons

Sofia Pavanello, Laura Dioni, Mirjam Hoxha, Ugo Fedeli, Danuta Mielzynska-Švach, Andrea A. Baccarelli

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Abstract

Background: Increased mitochondrial DNA copy number (mtDNAcn) is a biologic response to mtDNA damage and dysfunction, predictive of lung cancer risk. Polycyclic aromatic hydrocarbons (PAHs) are established lung carcinogens and may cause mitochondrial toxicity. Whether PAH exposure and PAH-related nuclear DNA (nDNA) genotoxic effects are linked with increased mtDNAcn has never been evaluated. Methods: We investigated the effect of chronic exposure to PAHs on mtDNAcn in peripheral blood lymphocytes (PBLs) of 46 Polish male noncurrent smoking coke-oven workers and 44 matched controls, who were part of a group of 94 study individuals examined in our previous work. Subjects' PAH exposure and genetic alterations were characterized through measures of internal dose (urinary 1-pyrenol), target dose [antibenzo[ a]pyrene diolepoxide (anti-BPDE)-DNA adduct], genetic instability (micronuclei and telomere length), and DNA methylation (p53 promoter) in PBLs. mtDNAcn (MT/S) was measured using a validated real-time PCR method. Results: Workers with PAH exposure above the median value (>3 mmol 1-pyrenol/mol creatinine) showed highermtDNAcn[geometric means (GM) of 1.06 (unadjusted) and 1.07 (age-adjusted)] compared with controls [GM 0.89 (unadjusted); 0.89 (age-adjusted); (P = 0.029 and 0.016)], as well as higher levels of genetic and chromosomal [i.e., anti-BPDE-DNA adducts (P <0.001), micronuclei (P <0.001), and telomere length (P=0.053)] and epigenetic [i.e., p53 gene-specific promoter methylation (P <0.001)] alterations in the nDNA. In the whole study population, unadjusted and age-adjusted mtDNAcn was positively correlated with 1-pyrenol (P = 0.043 and 0.032) and anti-BPDE-DNA adducts (P = 0.046 and 0.049). Conclusions:PAHexposure and PAH-relatednDNAgenotoxicity are associated with increased mtDNAcn. Impact: The present study is suggestive of potential roles of mtDNAcn in PAH-induced carcinogenesis.

Original languageEnglish
Pages (from-to)1722-1729
Number of pages8
JournalCancer Epidemiology Biomarkers and Prevention
Volume22
Issue number10
DOIs
Publication statusPublished - Oct 2013

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Polycyclic Aromatic Hydrocarbons
Mitochondrial DNA
DNA Adducts
Telomere
Coke
Lymphocytes
DNA
p53 Genes
DNA Methylation
Epigenomics
Carcinogens
Methylation
Real-Time Polymerase Chain Reaction
Lung Neoplasms
Creatinine
Carcinogenesis
Smoking
Lung
Population

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Mitochondrial dna copy number and exposure to polycyclic aromatic hydrocarbons. / Pavanello, Sofia; Dioni, Laura; Hoxha, Mirjam; Fedeli, Ugo; Mielzynska-Švach, Danuta; Baccarelli, Andrea A.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 22, No. 10, 10.2013, p. 1722-1729.

Research output: Contribution to journalArticle

Pavanello, Sofia ; Dioni, Laura ; Hoxha, Mirjam ; Fedeli, Ugo ; Mielzynska-Švach, Danuta ; Baccarelli, Andrea A. / Mitochondrial dna copy number and exposure to polycyclic aromatic hydrocarbons. In: Cancer Epidemiology Biomarkers and Prevention. 2013 ; Vol. 22, No. 10. pp. 1722-1729.
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abstract = "Background: Increased mitochondrial DNA copy number (mtDNAcn) is a biologic response to mtDNA damage and dysfunction, predictive of lung cancer risk. Polycyclic aromatic hydrocarbons (PAHs) are established lung carcinogens and may cause mitochondrial toxicity. Whether PAH exposure and PAH-related nuclear DNA (nDNA) genotoxic effects are linked with increased mtDNAcn has never been evaluated. Methods: We investigated the effect of chronic exposure to PAHs on mtDNAcn in peripheral blood lymphocytes (PBLs) of 46 Polish male noncurrent smoking coke-oven workers and 44 matched controls, who were part of a group of 94 study individuals examined in our previous work. Subjects' PAH exposure and genetic alterations were characterized through measures of internal dose (urinary 1-pyrenol), target dose [antibenzo[ a]pyrene diolepoxide (anti-BPDE)-DNA adduct], genetic instability (micronuclei and telomere length), and DNA methylation (p53 promoter) in PBLs. mtDNAcn (MT/S) was measured using a validated real-time PCR method. Results: Workers with PAH exposure above the median value (>3 mmol 1-pyrenol/mol creatinine) showed highermtDNAcn[geometric means (GM) of 1.06 (unadjusted) and 1.07 (age-adjusted)] compared with controls [GM 0.89 (unadjusted); 0.89 (age-adjusted); (P = 0.029 and 0.016)], as well as higher levels of genetic and chromosomal [i.e., anti-BPDE-DNA adducts (P <0.001), micronuclei (P <0.001), and telomere length (P=0.053)] and epigenetic [i.e., p53 gene-specific promoter methylation (P <0.001)] alterations in the nDNA. In the whole study population, unadjusted and age-adjusted mtDNAcn was positively correlated with 1-pyrenol (P = 0.043 and 0.032) and anti-BPDE-DNA adducts (P = 0.046 and 0.049). Conclusions:PAHexposure and PAH-relatednDNAgenotoxicity are associated with increased mtDNAcn. Impact: The present study is suggestive of potential roles of mtDNAcn in PAH-induced carcinogenesis.",
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T1 - Mitochondrial dna copy number and exposure to polycyclic aromatic hydrocarbons

AU - Pavanello, Sofia

AU - Dioni, Laura

AU - Hoxha, Mirjam

AU - Fedeli, Ugo

AU - Mielzynska-Švach, Danuta

AU - Baccarelli, Andrea A.

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N2 - Background: Increased mitochondrial DNA copy number (mtDNAcn) is a biologic response to mtDNA damage and dysfunction, predictive of lung cancer risk. Polycyclic aromatic hydrocarbons (PAHs) are established lung carcinogens and may cause mitochondrial toxicity. Whether PAH exposure and PAH-related nuclear DNA (nDNA) genotoxic effects are linked with increased mtDNAcn has never been evaluated. Methods: We investigated the effect of chronic exposure to PAHs on mtDNAcn in peripheral blood lymphocytes (PBLs) of 46 Polish male noncurrent smoking coke-oven workers and 44 matched controls, who were part of a group of 94 study individuals examined in our previous work. Subjects' PAH exposure and genetic alterations were characterized through measures of internal dose (urinary 1-pyrenol), target dose [antibenzo[ a]pyrene diolepoxide (anti-BPDE)-DNA adduct], genetic instability (micronuclei and telomere length), and DNA methylation (p53 promoter) in PBLs. mtDNAcn (MT/S) was measured using a validated real-time PCR method. Results: Workers with PAH exposure above the median value (>3 mmol 1-pyrenol/mol creatinine) showed highermtDNAcn[geometric means (GM) of 1.06 (unadjusted) and 1.07 (age-adjusted)] compared with controls [GM 0.89 (unadjusted); 0.89 (age-adjusted); (P = 0.029 and 0.016)], as well as higher levels of genetic and chromosomal [i.e., anti-BPDE-DNA adducts (P <0.001), micronuclei (P <0.001), and telomere length (P=0.053)] and epigenetic [i.e., p53 gene-specific promoter methylation (P <0.001)] alterations in the nDNA. In the whole study population, unadjusted and age-adjusted mtDNAcn was positively correlated with 1-pyrenol (P = 0.043 and 0.032) and anti-BPDE-DNA adducts (P = 0.046 and 0.049). Conclusions:PAHexposure and PAH-relatednDNAgenotoxicity are associated with increased mtDNAcn. Impact: The present study is suggestive of potential roles of mtDNAcn in PAH-induced carcinogenesis.

AB - Background: Increased mitochondrial DNA copy number (mtDNAcn) is a biologic response to mtDNA damage and dysfunction, predictive of lung cancer risk. Polycyclic aromatic hydrocarbons (PAHs) are established lung carcinogens and may cause mitochondrial toxicity. Whether PAH exposure and PAH-related nuclear DNA (nDNA) genotoxic effects are linked with increased mtDNAcn has never been evaluated. Methods: We investigated the effect of chronic exposure to PAHs on mtDNAcn in peripheral blood lymphocytes (PBLs) of 46 Polish male noncurrent smoking coke-oven workers and 44 matched controls, who were part of a group of 94 study individuals examined in our previous work. Subjects' PAH exposure and genetic alterations were characterized through measures of internal dose (urinary 1-pyrenol), target dose [antibenzo[ a]pyrene diolepoxide (anti-BPDE)-DNA adduct], genetic instability (micronuclei and telomere length), and DNA methylation (p53 promoter) in PBLs. mtDNAcn (MT/S) was measured using a validated real-time PCR method. Results: Workers with PAH exposure above the median value (>3 mmol 1-pyrenol/mol creatinine) showed highermtDNAcn[geometric means (GM) of 1.06 (unadjusted) and 1.07 (age-adjusted)] compared with controls [GM 0.89 (unadjusted); 0.89 (age-adjusted); (P = 0.029 and 0.016)], as well as higher levels of genetic and chromosomal [i.e., anti-BPDE-DNA adducts (P <0.001), micronuclei (P <0.001), and telomere length (P=0.053)] and epigenetic [i.e., p53 gene-specific promoter methylation (P <0.001)] alterations in the nDNA. In the whole study population, unadjusted and age-adjusted mtDNAcn was positively correlated with 1-pyrenol (P = 0.043 and 0.032) and anti-BPDE-DNA adducts (P = 0.046 and 0.049). Conclusions:PAHexposure and PAH-relatednDNAgenotoxicity are associated with increased mtDNAcn. Impact: The present study is suggestive of potential roles of mtDNAcn in PAH-induced carcinogenesis.

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